This application proposes to merge the work presently supported by three separate grants dealing with various aspects of work on polyoma virus. Molecular biological studies of polyoma virus interactions with susceptible cells in culture are being pursued with the particular goal of understanding the roles of the middle T and small T proteins in cell transformation and in productive viral infection. Structure-function studies of middle T using oligonucleotide mutagenesis are proposed, with the aim of elucidating the interaction of this viral protein with cellular protein kinases, and possibly with phospholipid metabolism. With respect to the virus growth cycle, similar approaches are being used to study VP/1 and its phosphorylation sites in order to gain a better understanding of how such modifications of the major capsid protein may be important in assembly of the virus particle. A third area deals with interactions of the virus with the intact host, in particular with the immune system and recognition of the polyoma-specific transplantation antigens.